Aconitase

protein
Name = aconitase 1, soluble
caption =


width =
HGNCid = 117
Symbol = ACO1
AltSymbols = IREB1
EntrezGene = 48
OMIM = 100880
RefSeq = NM_002197
UniProt = P21399
PDB =
ECnumber = 4.2.1.3
Chromosome = 9
Arm = p
Band = 21.1
LocusSupplementaryData = protein
Name = aconitase 2, mitochondrial
caption =


width =
HGNCid = 118
Symbol = ACO2
AltSymbols =
EntrezGene = 50
OMIM = 100850
RefSeq = NM_001098
UniProt = Q99798
PDB =
ECnumber = 4.2.1.3
Chromosome = 22
Arm = q
Band = 13.2
LocusSupplementaryData =

Aconitase (aconitate hydratase; EC [http://www.expasy.org/cgi-bin/get-enzyme-entry?4.2.1.3 4.2.1.3] ) is an enzyme that catalyses the stereo-specific isomerization of citrate to isocitrate via "cis"-aconitate in the tricarboxylic acid cycle, a non-redox-active process.

Function

By contrast with the majority of iron-sulfur proteins that function as electron carriers, the iron-sulfur cluster of aconitase reacts directly with an enzyme substrate. Aconitase has an active [Fe₄S₄] ²⁺ cluster, which may convert to an inactive [Fe₃S₄] ⁺ form. Three cysteine (Cys) residues have been shown to be ligands of the [Fe₄S₄] centre. In the active state, the labile iron ion of the [Fe₄S₄] cluster is not coordinated by Cys but by water molecules.

The iron-responsive element binding protein (IRE-BP) and 3-isopropylmalate dehydratase (α-isopropylmalate isomerase; EC [http://www.expasy.org/cgi-bin/get-enzyme-entry?4.2.1.33 4.2.1.33] ), an enzyme catalysing the second step in the biosynthesis of leucine, are known aconitase homologues. Iron regulatory elements (IREs) constitute a family of 28-nucleotide, non-coding, stem-loop structures that regulate iron storage, heme synthesis and iron uptake. They also participate in ribosome binding and control the mRNA turnover (degradation). The specific regulator protein, the IRE-BP, binds to IREs in both 5' and 3' regions, but only to RNA in the apo form, without the Fe-S cluster. Expression of IRE-BP in cultured cells has revealed that the protein functions either as an active aconitase, when cells are iron-replete, or as an active RNA-binding protein, when cells are iron-depleted. Mutant IRE-BPs, in which any or all of the three Cys residues involved in Fe-S formation are replaced by serine, have no aconitase activity, but retain RNA-binding properties.

Aconitase is inhibited by fluoroacetate, therefore fluoroacetate is poisonous.

References

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External links

* [http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=7ACN 7ACN] - PDB structure of pig aconitase in complex with [Fe₄S₄] cluster and isocitrate
* [http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1L5J 1L5J] - PDB structure of "Escherichia coli" aconitase complexed with [Fe₃S₄] cluster and aconitate
* [http://www.ebi.ac.uk/interpro/IEntry?ac=IPR000573 IPR000573] - [http://www.ebi.ac.uk/interpro/ InterPro] entry for aconitase
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